4.0SQUARESQUARESQUARESQUARESQUAREinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveinactiveMesenteric Lymph NodesGerminal centerLumenEpithelium Lamina propria
T helper 1 cells represent an effector subset of CD4+ T cells involved in the cellular immune response and host defense against intracellular pathogens. They are centrally involved in cell-mediated immunity and the production of complement fixing antibodies. Moreover, they are characterized by the production of pro-inflammatory cytokines like interferon-γ (IFN-γ) and interleukin-2 (IL-2), which stimulate the phagocytosis and destruction of intracellular microbial pathogens by macrophages and other lymphocytes.
PMID: 10441214
PMID: 9529145
insideSIMPLE_MOLECULETh1
T helper type 2 cells represent an effector subset of CD4+ T cells that are involved in the humoral immune response and host defense against extracellular parasites by enhancing mucus production on the endothelial surfaces. These cells are characterized by the production of several cytokines including interleukin 4, which generally stimulates the production of antibodies targeting large extracellular parasites.
PMID: 10441214
PMID: 9529145
insideSIMPLE_MOLECULETh2
T helper 17 cells are a subset of effector CD4+ T helper cells that produce interleukin-17 (IL-17) and exhibit effector functions such as clearance of pathogens. Macrophages and dendritic cells infected with Escherichia coli favor Th17 responses. The presence of IL-17-producing cells in the gut is associated with immune-mediated disorders such as inflammatory bowel disease.
PMID: 16200070
PMID: 16990136
PMID: 19132915
PMID: 21112468
insideSIMPLE_MOLECULETh17
Induced regulatory T cells are CD4+ T cells, which are critical for the maintenance of immune cell homeostasis. They orchestrate immune responses by enforcing a dominant negative regulation on other immune cells and by suppressing pathogenic responses to both "self" and "non-self" antigens. Treg cells prevent an excessive inflammatory response at the gut mucosa.
PMID: 10837065
PMID: 19464985
PMID: 21775683
PMID: 18184698
insideSIMPLE_MOLECULETreginsideDEGRADEDs23insideDEGRADEDs24
Epithelial cells that have been in contact with Clostridium difficile. Epithelial cells are the organism's first line of defense by preventing the entry of potentially dangerous microorganisms.
PMID: 15821737
insideSIMPLE_MOLECULEEp
Classically activated macrophages are potent effector cells that produce proinflammatory cytokines in response to a type 1 cytokine environment or upon recognition of pathogen-associated molecular patterns. M1 macrophages produce large amounts of interleukin-12 (IL-12) and therefore promote a T helper 1 (Th1) immune response.
PMID: 19696407
insideSIMPLE_MOLECULEM1
M2 macrophages, also known as "alternatively activated macrophages", are induced in response to T helper 2 (Th2) cytokine profiles and are involved in initiating and maintaining anti-inflammatory and regulatory responses. M2 macrophages counteract inflammatory responses and promote angiogenesis and tissue remodeling.
PMID: 16543403
PMID: 10878379
PMID: 21112468
insideSIMPLE_MOLECULEM2
Undifferentiated macrophages initiate an innate immune response against microbes following recognition of pathogen-associated molecular patterns through pattern-recognition receptors. After phagocytosis of pathogens, macrophages present the antigens to T cells and produce different molecules, thus leading to the expansion and differentiation of lymphocytes. Depending on the environmental signals macrophages can differentiate at least into two different subsets, M1 ("classic" activation) and M2 ("alternative" activation).
PMID: 17681149
PMID: 16920488
insideSIMPLE_MOLECULEM0insideDEGRADEDs29insideDEGRADEDs32insideDEGRADEDs33
Induced regulatory T cells are CD4+ T cells, which are critical for the maintenance of immune cell homeostasis. They orchestrate immune responses by enforcing a dominant negative regulation on other immune cells and by suppressing pathogenic responses to both "self" and "non-self" antigens. Treg cells prevent an excessive inflammatory response at the gut mucosa.
PMID: 10837065
PMID: 19464985
PMID: 21775683
PMID: 18184698
insideSIMPLE_MOLECULETreg Escherichia coli favor Th17 responses. The presence of IL-17-producing cells in the gut is associated with immune-mediated disorders such as inflammatory bowel disease.
PMID: 16200070
PMID: 16990136
PMID: 19132915
PMID: 21112468
insideSIMPLE_MOLECULETh17
T helper type 2 cells represent an effector subset of CD4+ T cells that are involved in the humoral immune response and host defense against extracellular parasites by enhancing mucus production on the endothelial surfaces. These cells are characterized by the production of several cytokines including interleukin 4, which generally stimulates the production of antibodies targeting large extracellular parasites.
PMID: 10441214
PMID: 9529145
insideSIMPLE_MOLECULETh2
T helper 1 cells represent an effector subset of CD4+ T cells involved in the cellular immune response and host defense against intracellular pathogens. They are centrally involved in cell-mediated immunity and the production of complement fixing antibodies. Moreover, they are characterized by the production of pro-inflammatory cytokines like interferon-γ (IFN-γ) and interleukin-2 (IL-2), which stimulate the phagocytosis and destruction of intracellular microbial pathogens by macrophages and other lymphocytes.
PMID: 10441214
PMID: 9529145
insideSIMPLE_MOLECULETh1
Naïve T cells are CD4+ T cells that have not entered in contact with antigen and can differentiate into distinct effector or regulatory subsets when activated by antigen presenting cells.
PMID: 10441214
PMID 19935802
insideSIMPLE_MOLECULEnT
Activated neutrophil
Neutrophilic granulocytes are white blood cells containing neutrally-stained granules, which are filled with enzymes that help the cell to digest and kill phagocytosed microorganisms. During the acute phase of inflammation neutrophils are one of the first responders who migrate towards the site of inflammation in response to chemical signals such as interleukin-8.
pmid: 10830774
pmid: 16498448
pmid: 19390567
pmid: 18405381
insideSIMPLE_MOLECULEActivated neutrophilinsideDEGRADEDs23
Epithelial cells are the organism's first line of defense by preventing the entry of potentially dangerous microorganisms. Intestinal epithelial cells are continuously exposed to large numbers of commensal bacteria but are relatively insensitive to them. However, following contact with pathogens they produce inflammatory mediators.
PMID: 15821737
insideSIMPLE_MOLECULEEEscherichia coli infection triggers inflammation and apoptosis of epithelial cells.
PMID: 10417197
insideSIMPLE_MOLECULEDead E
Interleukin 2 (IL-2) induces CD4+ T cell proliferation. Its signaling through CD25 (IL-2R) activates the transcription factor STAT5, which is responsible for the induction of the CD4+ T helper type 2 and CD4+ regulatory T cell phenotypes. IL-2 also contributes to the production of interleukin-10 (IL-10) in CD4+ T cells via STAT5.
PDB: 1Z92
PMID: 19348914
insideSIMPLE_MOLECULEIL-2
Effector dendritic cells are professional antigen presenting cellsable to induce T cell-dependent effector responses such as T helper 1 (Th1) and Th17 responses.
PMID: 10544185
insideSIMPLE_MOLECULEeDC
Dendritic cells are located at sites of pathogen entry in the gastrointestinal mucosa and recognize two signals that lead to the activation of both DC- and T helper 1 cell (Th1)-mediated immunity: 1. pathogen-associated molecular patterns from bacteria and 2. the inflammatory signals derived from inflamed epithelial cells. Immature DC are professional antigen-presenting cells with the capacity to internalize and process antigens. They present antigens via the MHC-class II pathway but cannot prime immune responses.
PMID: 11773610
PMID: 16691244
PMID: 17378762
insideSIMPLE_MOLECULEiDC
Interleukin-4 is a cytokine secreted by M2 macrophages and effector dendritic cells that induces the differentiation of naïve T cells to a T cell type 2 phenotype. Th2 cells themselves produce IL-4, which can induce proliferation of B-cells and subsequently antibody production (i.e. immunoglobulin A), thereby promoting humoral immunity. IL-4 is counteracting IFN-γ and down regulates the differentiation of Th1 cells.
PDB: 3BPL
PMID: 8893001
PMID: 18988742
insideSIMPLE_MOLECULEIL-4
Interleukin-17 (IL-17) is a cytokine secreted by activated CD4+ T helper type 17 cells responsible for inducing and regulating proinflammatory responses by recruiting monocytes and neutrophils to the site of inflammation.
PDB: 2VXS
insideSIMPLE_MOLECULEIL-17
Interleukin-8 is secreted by epithelial cells which have been exposed to inflammatory stimuli. It is involved in recruitment and activation of neutrophils.
PMID: 1639201
PDB: 3IL8
insideSIMPLE_MOLECULEIL-8insideDEGRADEDs100
Interleukin 10 (IL-10) is a cytokine with broad anti-inflammatory properties that is secreted by T helper type 1 (Th1) and regulatory T cells (Treg). It can block the activation of cytokine synthesis and suppress the effector functions of macrophages, T cells and NK cells. In addition, IL-10 contributes to the regulation of proliferation and differentiation of B cells, mast cells and thymocytes.
PDB: 2H24
PMID: 8386517
insideSIMPLE_MOLECULEIL-10
Interleukin-17 (IL-17) is a cytokine secreted by activated CD4+ T helper type 17 cells responsible for inducing and regulating proinflammatory responses by recruiting monocytes and neutrophils to the site of inflammation.
PDB: 2VXS
insideSIMPLE_MOLECULEIL-17
Effector dendritic cells are professional antigen presenting cellsable to induce T cell-dependent effector responses such as T helper 1 (Th1) and Th17 responses.
PMID: 10544185
insideSIMPLE_MOLECULEeDC
Interleukin-12 is a cytokine naturally produced by effector dendritic cells and M1 macrophages in response to antigenic stimulation. IL-12 is involved in the differentiation of naïve T cells into effector T helper 1 cells. In combination with IL-18 and IFN-γ, IL-12 synergizes to induce a lineage commitment towards Th1.
PDB: 3HMX
PMID: 9200435
insideSIMPLE_MOLECULEIL-12
Interleukin-6 is a cytokine secreted by T cells and M1 macrophages in response to specific microbial products. In combination with TGF-β, IL-6 contributes to the induction of Th17 cells by activating STAT3.
PDB: 1ALU
insideSIMPLE_MOLECULEIL-6
Interleukin-18 exerts potent IFN-γ inducing activities and together with IL-12 it plays an important role in the Th1-mediated immune response.
PDB: 3LTQ
PMID: 9638361
PMID: 10679398
insideSIMPLE_MOLECULEIL-18
Interleukin-4 is a cytokine secreted by M2 macrophages and effector dendritic cells that induces the differentiation of naïve T cells to a T cell type 2 phenotype. Th2 cells themselves produce IL-4, which can induce proliferation of B-cells and subsequently antibody production (i.e. immunoglobulin A), thereby promoting humoral immunity. IL-4 is counteracting IFN-γ and down regulates the differentiation of Th1 cells.
PDB: 3BPL
PMID: 8893001
PMID: 18988742
insideSIMPLE_MOLECULEIL-4
Non-activated neutrophil
Neutrophilic granulocytes are white blood cells containing neutrally-stained granules, which are filled with enzymes thatallow the digestion of phagocytosed microorganisms. During the acute phase of inflammation neutrophils are one of the first responders who migrate towards the site of inflammation in response to chemical signals such as interleukin-8.
pmid: 10830774
pmid: 16498448
pmid: 19390567
pmid: 18405381
insideSIMPLE_MOLECULENon-activated neutrophil
Plasma cells are white blood cells which are characterized by the production of antibodies. Like all blood cells, plasma cells ultimately originate in the bone marrow. However, these cells leave the bone marrow as B cells before they terminally differentiate into plasma cells within lymph nodes.
insideSIMPLE_MOLECULEPlasma cell
IgA
Immunoglobulin A (IgA) is an antibody that plays a critical role in mucosal immunity. It is produced by plasma cells in the lamina propria. Once in the blood, IgA interacts with the Fc receptor FcαRI to initiate inflammatory reactions: antibody-dependent cell-mediated cytotoxicity (ADCC); degranulation of eosinophils and basophils; phagocytosis by monocytes, macrophages, neutrophils and eosinophils; and triggering of respiratory burst activity by polymorphonuclear leukocytes.
pmid: 16611558
pmid: 12511876
insideSIMPLE_MOLECULEIgA
IgA
Immunoglobulin A (IgA) is an antibody that plays a critical role in mucosal immunity. It is produced by plasma cells in the lamina propria. Once in the blood, IgA interacts with the Fc receptor FcαRI to initiate inflammatory reactions: antibody-dependent cell-mediated cytotoxicity (ADCC); degranulation of eosinophils and basophils; phagocytosis by monocytes, macrophages, neutrophils and eosinophils; and triggering of respiratory burst activity by polymorphonuclear leukocytes.
pmid: 16611558
pmid: 12511876
insideSIMPLE_MOLECULEIgA
TGF-β is a cytokine secreted by effector dendritic cells that contributes to immune regulation by down-regulating both Th1 and Th2 cell functions as well as triggering apoptosis. It also contributes to Th17 induction in the presence of IL-6.
PDB: 3FAA
PMID: 10611753
insideSIMPLE_MOLECULETGFβ
TGF-β is a cytokine secreted by effector dendritic cells that contributes to immune regulation by down-regulating both Th1 and Th2 cell functions as well as triggering apoptosis. It also contributes to Th17 induction in the presence of IL-6.
PDB: 3FAA
PMID: 10611753
insideSIMPLE_MOLECULETGFβ
Interferon-γ (INF-γ) is a cytokine secreted by activated CD4+ T helper type 1 (Th1) cells. Th1 cells have three key functions: 1) macrophage activation and enhancement of their antimicrobial actions, 2) increase of MHC expression, and 3) promotion of cell-mediated immunity. IFN-γ inhibits CD4+ T helper type 2 (Th2) differentiation, thereby facilitating cross-regulation between Th1 and Th2 cells.
PDB: 3BES
PMID: 8893001
PMID: 8379463
insideSIMPLE_MOLECULEIFNɣ
imB
Immature B cells are produced in the bone marrow of most mammals. After reaching the IgM+ immature stage in the bone marrow, they migrate to the spleen, where some of them differentiate into mature B lymphocytes.
pmid: 14962193
insideSIMPLE_MOLECULEimB
Mature B cells are lymphocytes that play an important role in the humoral immune response. Their principal functions are to produce antibodies against antigens, to act as antigen-presenting cells (APCs) and eventually develop into memory B cells after activation by antigen interaction.
pmid: 14962193
insideSIMPLE_MOLECULEmB
T helper 2 cells represent an effector subset of CD4+ T cells that are involved in the humoral immune response and host defense against extracellular parasites by enhancing mucus production on the endothelial surfaces. These cells are characterized by the production of several cytokines including interleukin 4, which generally stimulates the production of antibodies targeting large extracellular parasites.
pmid: 10441214
pmid: 9529145
insideSIMPLE_MOLECULETh2insideDEGRADEDpIL-8insideDEGRADEDpIgAinsideDEGRADEDpIL-10insideDEGRADEDpIFNginsideDEGRADEDpIL-4insideDEGRADEDpIL-17insideDEGRADEDpTGFBinsideDEGRADEDpIL-2insideDEGRADEDpIL-12insideDEGRADEDpIL-18insideDEGRADEDpIL-4insideDEGRADEDpIL-6insideDEGRADEDpIFNginsideDEGRADEDpIL-10insideDEGRADEDpIL-17insideDEGRADEDpTGFbinsideDEGRADEDpIL-2
Interleukin 2 (IL-2) induces CD4+ T cell proliferation. Its signaling through CD25 (IL-2R) activates the transcription factor STAT5, which is responsible for the induction of the CD4+ T helper type 2 and CD4+ regulatory T cell phenotypes. IL-2 also contributes to the production of interleukin-10 (IL-10) in CD4+ T cells via STAT5.
PDB: 1Z92
PMID: 19348914
insideSIMPLE_MOLECULEIL-2
Epithelial cells can secrete TNF-alpha in response to bacterial invasion.
PMCID: PMC295369
insideSIMPLE_MOLECULETNF-αinsideDEGRADEDpTNF-αinsideDEGRADEDs99insideDEGRADEDpIL-1B
Interleukin 10 (IL-10) is a cytokine with broad anti-inflammatory properties that is secreted by T helper type 1 (Th1) and regulatory T cells (Treg). It can block the activation of cytokine synthesis and suppress the effector functions of macrophages, T cells and NK cells. In addition, IL-10 contributes to the regulation of proliferation and differentiation of B cells, mast cells and thymocytes.
PDB: 2H24
PMID: 8386517
insideSIMPLE_MOLECULEIL-10
Interferon-γ (INF-γ) is a cytokine secreted by activated CD4+ T helper type 1 (Th1) cells. Th1 cells have three key functions: 1) macrophage activation and enhancement of their antimicrobial actions, 2) increase of MHC expression, and 3) promotion of cell-mediated immunity. IFN-γ inhibits CD4+ T helper type 2 (Th2) differentiation, thereby facilitating cross-regulation between Th1 and Th2 cells.
PDB: 3BES
PMID: 8893001
PMID: 8379463
insideSIMPLE_MOLECULEIFNɣ
Interleukin 1 β (IL-1β) is a cytokine produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis.
insideSIMPLE_MOLECULEIL-1β
Effector memory T cells are a T cell subset that has rapidly acquired effector functions to destroy infected cells and/or secrete inflammatory cytokines that inhibit replication of the pathogen. They can also enhance B-cell responses and CD8+ T-cell development through the activation of antigen presenting cells or secretion of cytokines.
PMID: 12001996
PMID: 15032595
insideSIMPLE_MOLECULEemTinsideDEGRADEDs100insideDEGRADEDpTGFbinsideDEGRADEDpIL-12
Interleukin-12 is a cytokine naturally produced by effector dendritic cells and M1 macrophages in response to antigenic stimulation. IL-12 is involved in the differentiation of naïve T cells into effector T helper 1 cells. In combination with IL-18 and IFN-γ, IL-12 synergizes to induce a lineage commitment towards Th1.
PDB: 3HMX
PMID: 9200435
insideSIMPLE_MOLECULEIL-12
Interleukin-6 is a cytokine secreted by T cells and M1 macrophages in response to specific microbial products. In combination with TGF-β, IL-6 contributes to the induction of Th17 cells by activating STAT3.
PDB: 1ALU
insideSIMPLE_MOLECULEIL-6
Monocyte chemoattractant protein 1 is secreted predominantly by classically activated macrophages and acts as a T cell chemoattractant.
pmid: 8170963
insideSIMPLE_MOLECULEMCP-1insideDEGRADEDpMCP-1
Immunoglobulin M (IgM) is an antibody that plays a critical role in mucosal immunity. It is produced by plasma cells in the lamina propria. Once in the blood, IgM is particularly effective at complement activation. By itself, IgM is an ineffective opsonin; however it contributes greatly to opsonization by activating complement and causing C3b to bind to the antigen and their toxins.
PMID: 941799
insideSIMPLE_MOLECULEIgM
Immunoglobulin G (IgG) is an antibody that plays a critical role in mucosal immunity. It is produced by plasma cells in the lamina propria. It can bind to many kinds of pathogens, for example viruses, bacteria, and fungi, and protects the body against them by agglutination and immobilization, complement activation (classical pathway), opsonization for phagocytosis, and neutralization of their toxins. It also plays an important role in Antibody-dependent cell-mediated cytotoxicity(ADCC) and Intracellular antibody-mediated proteolysis.
PMID: 21045130
insideSIMPLE_MOLECULEIgG
Toxin B secreted by C difficile is a cytotoxin that enters the cells by endocytosis and induce disruption of epithelial tight junctions, as well as an intense inflammatory response characterized by infiltration and recruitment of circulating immune cells in the gut, especially neutrophils and macrophages. Moreover, it induces secretion of inflammatory chemokines and cytokines such as IL-8 and TNF-α. Both toxin A and toxin B deactivate small GTPases such as Rho, Rac and Cdc42 by glucosylation of a threonine residue. Inhibition of these GTPases causes the shutdown of signal transduction cascades leading to: depolymerization of the cytoskeleton, gene transcription of certain stress-activated protein kinases, a drop in synthesis of phosphatidylinositol 4,5 bisphosphate and possibly even the loss of cell polarity.Loss of cytoskeletal structure results in cell rounding, and this loss of structure may account for the host’s reaction to C. difficile.
PMID: 3949240
PMID: 15831824
insideSIMPLE_MOLECULEToxin BClostridium difficile typically is a harmless environmental sporulated gram-positive anaerobic bacterium, but has recently re-emerged as a significant pathogen that can cause nosocomial diarrhea, colitis and even death, particularly after antibiotic treatment. C. difficile grows in the intestine of individuals whose commensal microflora has been altered due to an antimicrobial drug therapy, administration of immunosuppressants, cytostatic agents and proton pump inhibitors (PPI). The organism colonizes the intestinal tract and produces two toxins of relevance to the disease pathogenesis: an enterotoxin (toxin A or TcdA) and a cytotoxin (toxin B or TcdB).
PMID: 20424299
PMID: 19340897
PMID: 3949240
PMID: 18848941
PMID: 915343
PMID: 630301
PMID: 20653067
PMID: 12746372
PMID: 2115017
insideSIMPLE_MOLECULECdiffinsideDEGRADEDpTNF-α
Toxin B secreted by C difficile is a cytotoxin that enters the cells by endocytosis and induce disruption of epithelial tight junctions, as well as an intense inflammatory response characterized by infiltration and recruitment of circulating immune cells in the gut, especially neutrophils and macrophages. Moreover, it induces secretion of inflammatory chemokines and cytokines such as IL-8 and TNF-α. Both toxin A and toxin B deactivate small GTPases such as Rho, Rac and Cdc42 by glucosylation of a threonine residue. Inhibition of these GTPases causes the shutdown of signal transduction cascades leading to: depolymerization of the cytoskeleton, gene transcription of certain stress-activated protein kinases, a drop in synthesis of phosphatidylinositol 4,5 bisphosphate and possibly even the loss of cell polarity.Loss of cytoskeletal structure results in cell rounding, and this loss of structure may account for the host’s reaction to C. difficile.
PMID: 3949240
PMID: 15831824
insideSIMPLE_MOLECULEToxin B
Toxin A secreted by C difficile is an enterotoxin that causes fluid accumulation along with
C. difficile.
PMID: 3949240
insideSIMPLE_MOLECULEToxin A
Effector memory T cells differentiate into T helper 1 cells (Th1).
PMID: 15032595
emT differenciation into Th1STATE_TRANSITIONsa12sa15sa210sa209sa224sa105
Effector memory T cells differentiate into T helper 2 cells (Th2).
PMID: 15032595
emT differenciation into Th2STATE_TRANSITIONsa12sa16sa211sa210sa223sa212sa218
Effector memory T cells differentiate into T helper 17 cells (Th17).
PMID: 15032595
emT differenciation into Th17STATE_TRANSITIONsa12sa19sa208sa740
Effector memory T cells differentiate into CD4+ T regulatory cells (iTreg).
PMID: 15032595
emT differenciation into TregSTATE_TRANSITIONsa12sa21sa212sa225EAEC deathSTATE_TRANSITIONsa4sa28Neutrophil activationSTATE_TRANSITIONsa11sa30sa96sa714sa105Th1 cell deathSTATE_TRANSITIONsa15sa23Th2 cell deathSTATE_TRANSITIONsa16sa26Th17 cell deathSTATE_TRANSITIONsa19sa25Treg cell deathSTATE_TRANSITIONsa21sa24
Macrophages differentiate into a M1 phenotype in the presence of IFN-γ alone or in combination with microbial stimuli.
PMID: 18467122
PMID: 10072066
M0 differenciation into M1STATE_TRANSITIONsa34sa32sa105sa7
Macrophages differentiate into a M2 phenotype in the presence of IL-4, IL-10 and TGF-β.
PMID: 18467122
PMID: 10072066
M0 differenciation into M2STATE_TRANSITIONsa34sa33sa103sa104sa211sa225sa7sa215STATE_TRANSITIONsa34sa35M0 cell deathSTATE_TRANSITIONsa35sa34sa29M2 cell deathSTATE_TRANSITIONsa33sa38STATE_TRANSITION0.3901405409810037,-2.1573902417415525E-5sa32sa33sa105sa746sa749STATE_TRANSITIONsa33sa32sa105sa746sa749M1 cell deathSTATE_TRANSITIONsa32sa39
Naïve CD4+ T cells can differentiate into different effector CD4+ T cell subsets (i.e. Th1, Th2 or Th17) or induced regulatory T cells (iTreg) depending on the cytokine environment during stimulation by antigen presenting cells (APC). CD4+ T cells need two signals for activation: 1. the interaction of the antigenic peptide-MHC class II complex with the TCR-CD3 complex, 2. a non-specific co-stimulatory signal provided by the interaction of CD28 or CTLA-4 on T cells with B7 molecules on APCs. A naïve CD4+ T cell will differentiate into a T helper 1 (Th1) phenotype when stimulated with interferon-γ (INF-γ) and interleukin-12 (IL-12).
PMID: 15961574
PMID: 12932290
PMID: 10441214
PMID: 9529145
PMID: 12147631
nT differenciation into Th1STATE_TRANSITIONsa50sa47sa85sa736
Naïve CD4+ T cells can differentiate into different effector CD4+ T cell subsets (i.e. Th1, Th2 or Th17) or induced regulatory T cells (iTreg) depending on the cytokine environment during stimulation by antigen presenting cells (APC). CD4+ T cells need two signals for activation: 1. the interaction of the antigenic peptide-MHC class II complex with the TCR-CD3 complex, 2. a non-specific co-stimulatory signal provided by the interaction of CD28 or CTLA-4 on T cells with B7 molecules on APCs. A naïve CD4+ T cell will differentiate into a T helper 2 (Th2) phenotype when stimulated with interleukin-4 (IL-4) and interleukin-2 (IL-2).
PMID: 15961574
PMID: 12932290
PMID: 10441214
PMID: 9529145
PMID: 12147631
nT differenciation into Th2STATE_TRANSITIONsa50sa44sa93sa84sa737
Naïve CD4+ T cells can differentiate into different effector CD4+ T cell subsets (i.e. Th1, Th2 or Th17) or induced regulatory T cells (iTreg) depending on the cytokine environment during stimulation by antigen presenting cells (APC). CD4+ T cells need two signals for activation: 1. the interaction of the antigenic peptide-MHC class II complex with the TCR-CD3 complex, 2. a non-specific co-stimulatory signal provided by the interaction of CD28 or CTLA-4 on T cells with B7 molecules on APCs. A naïve CD4+ T cell will differentiate into a T helper 17 (Th17) phenotype when stimulated with transforming growth factor β (TGF-β) and interleukin-6 (IL-6).
PMID: 17569825
PMID: 21831771
nT differenciation into Th17STATE_TRANSITIONsa50sa42sa94sa97sa738
Naïve CD4+ T cells can differentiate into different effector CD4+ T cell subsets (i.e. Th1, Th2 or Th17) or induced regulatory T cells (iTreg) depending on the cytokine environment after stimulation by antigen presenting cells. CD4+ T cells need two signals for activation: 1. the interaction of the antigenic peptide-MHC class II complex with the TCR-CD3 complex, 2. a non-specific co-stimulatory signal provided by the interaction of CD28 or CTLA-4 on T cells with B7 molecules on APCs. A naïve CD4+ T cell will differentiate into an iTreg phenotype when stimulated with transforming growth factor β (TGF-β) and interleukin-2 (IL-2).
PMID: 17569825
PMID: 12612578
PMID: 12522256
nT differenciation into TregSTATE_TRANSITIONsa50sa40sa84sa97sa734STATE_TRANSITIONsa51sa50STATE_TRANSITIONsa42sa40sa94sa97STATE_TRANSITIONsa40sa42sa94sa97STATE_TRANSITIONsa19sa21sa106sa104sa103Th17-Treg plasticitySTATE_TRANSITIONsa21sa19sa106sa104sa208sa103
Induced CD4+ regulatory T cells produce interleukin-2 (IL-2), which represents a key signal contributing to the growth and survival of cytotoxic T cells, the development of T cell immunologic memory and the development of regulatory T cells.
PMID: 18693266
PMID: 19348914
PMID: 18726679
IL-2 production by TregTRANSLATIONsa689sa84sa40
Induced CD4+ regulatory T (iTreg) cells secrete transforming growth factor-β, a cytokine that plays a critical role in the regulation of immune function.
PMID: 16146793
TGF-β production by TregTRANSLATIONsa688sa97sa40eDC deathSTATE_TRANSITIONsa87sa100Epithelial cells deathSTATE_TRANSITIONsa29sa80STATE_TRANSITIONsa764sa80Epithelial cells deathSTATE_TRANSITIONsa80sa764STATE_TRANSITIONsa764sa29sa4sa645sa758Epithelial cells contacts the antigenSTATE_TRANSITIONsa29sa764
CD4+ induced regulatory T cells (iTreg) produce interleukin-10.
PMID: 15545984
PMID: 15286781
PMID: 16903904
IL-10 production by TregTRANSLATIONsa708sa103sa21
Each T-cell subset produces cytokines that serve as its own autocrine growth factor. CD4+ T helper type 1 (Th1) cells produce interferon-γ, which amplifies Th1 development and inhibits proliferation of the CD4+ T helper type 2 (Th2) subset.
PMID: 2949327
PMID: 8476563
PMID: 10064070
IFNɣ production by Th1TRANSLATIONsa701sa105sa211sa15
Immature dendritic cells become activated and acquire their full functionality in response to danger signals such as pathogen associated molecular patterns. This maturation process leads to de novo or increased expression of surface markers involved in activation, maturation and co-stimulation. Furthermore, mature dendritic cells (mDC) migrate to the mesenteric lymph node where they present antigens to T cells and thus induce effector immune responses.
PMID: 10544185
TRANSPORT0.07290197355180783,0.14748701682016224 1.0013516237385085,0.1140213180052842sa87sa732IL-12 production by M1STATE_TRANSITIONsa697sa210sa32IL-18 production by M1STATE_TRANSITIONsa698sa209sa32IL-6 production by M1STATE_TRANSITIONsa700sa208sa32
Each T-cell subset produces cytokines that serve as its own autocrine growth factor. CD4+ T helper type 2 cells (Th2) produce interleukin-4, which amplifies Th2 development and inhibits proliferation of CD4+ T helper type 1 (Th1) cells.
PMID: 2949327
PMID: 11751746
IL-4 production by Th2STATE_TRANSITIONsa705sa211sa16sa105
Induced CD4+ regulatory T cells produce interleukin-2 (IL-2), which represents a key signal contributing to the growth and survival of cytotoxic T cells, the development of T cell immunologic memory and the development of regulatory T cells.
PMID: 18693266
PMID: 19348914
PMID: 18726679
IL-2 production by TregSTATE_TRANSITIONsa709sa212sa21
CD4+ T helper type 1 (Th1) cells produce interleukin-10.
PMID: 19646904
PMID: 17283207
PMID: 7910138
PMID: 8419468
IL-10 production by Th1STATE_TRANSITIONsa704sa215sa15IL-4 production M2STATE_TRANSITIONsa699sa218sa33IL-4 production by eDCSTATE_TRANSITIONsa711sa223sa87IL-12 production by eDCSTATE_TRANSITIONsa712sa224sa87TGF- β production by eDCSTATE_TRANSITIONsa710sa225sa87
CD4+ T helper 17 (Th17) is a recently discovered lineage of T cells characterized by the ability to preferentially secrete the proinflammatory cytokine interleukin-17.
PMID: 17884812
PMID: 17994024
IL-17 production by Th17STATE_TRANSITIONsa706sa106sa19
CD4+ induced regulatory T cells (iTreg) produce interleukin-10.
PMID: 15545984
PMID: 15286781
PMID: 16903904
IL-10 production by TregSTATE_TRANSITIONsa690sa101sa40
Induced CD4+ regulatory T (iTreg) cells secrete transforming growth factor-β, a cytokine that plays a critical role in the regulation of immune function.
PMID: 16146793
TGF-β production by TregSTATE_TRANSITIONsa707sa104sa21
Immunoglobulin A (IgA) is produced by plasma cells in the lamina propria adjacent to mucosal surfaces. It binds to the polymeric immunoglobulin receptor on the surface of epithelial cells and is taken up into the cell via endocytosis. Finally, it is secreted on the luminal surface of the epithelial cells. In the gut, it can bind to the mucus layer on top of the epithelial cells to form a barrier capable of neutralizing antigens before they reach the cells.
PMID: 21816150
PMID: 1924341
TRANSPORT0.40299906256036977,0.509392104161658 0.9957053764196573,0.05359841791136513sa644sa645STATE_TRANSITIONsa649sa650sa670
Naïve and primed B cells migrate to mesenteric lymph nodes where they differentiate to plasma cells.
STATE_TRANSITIONsa650sa640STATE_TRANSITIONsa668sa96sa29sa728
Immunoglobulin A (IgA) is produced by plasma cells in the lamina propria adjacent to mucosal surfaces.
PMID: 21816150
PMID: 1924341
STATE_TRANSITIONsa669sa644sa640sa218sa211sa223TRANSPORTsa44sa670TRANSPORTsa670sa44
CD4+ T helper type 1 (Th1) cells produce interleukin-10.
PMID: 19646904
PMID: 17283207
PMID: 7910138
PMID: 8419468
IL-10 production by Th1STATE_TRANSITIONsa684sa217sa47
Each T-cell subset produces cytokines that serve as its own autocrine growth factor. CD4+ T helper type 1 (Th1) cells produce interferon-γ, which amplifies Th1 development and inhibits proliferation of the CD4+ T helper type 2 (Th2) subset.
PMID: 2949327
PMID: 8476563
PMID: 10064070
IFNɣ production by Th1STATE_TRANSITIONsa685sa85sa47sa93
Each T-cell subset produces cytokines that serve as its own autocrine growth factor. CD4+ T helper type 2 cells (Th2) produce interleukin-4, which amplifies Th2 development and inhibits proliferation of CD4+ T helper type 1 (Th1) cells.
PMID: 2949327
PMID: 11751746
STATE_TRANSITIONsa686sa93sa85sa44
CD4+ T helper 17 (Th17) is a recently discovered lineage of T cells characterized by the ability to preferentially secrete the proinflammatory cytokine interleukin-17.
PMID: 17884812
PMID: 17994024
STATE_TRANSITIONsa691sa94sa42STATE_TRANSITIONsa715sa714sa29STATE_TRANSITIONsa89sa87sa645STATE_TRANSITIONsa4sa723sa29STATE_TRANSITIONsa7sa722sa30sa32sa752sa754STATE_TRANSITIONsa28sa4sa4STATE_TRANSITIONsa729sa728sa32eDC deathSTATE_TRANSITIONsa732sa730IL-4 production by eDCSTATE_TRANSITIONsa733sa737sa732IL-12 production by eDCSTATE_TRANSITIONsa735sa736sa732TGF- β production by eDCSTATE_TRANSITIONsa731sa734sa732STATE_TRANSITIONsa739sa738sa732STATE_TRANSITIONsa741sa740sa87STATE_TRANSITIONsa747sa746sa33STATE_TRANSITIONsa748sa749sa33STATE_TRANSITIONsa751sa750sa32
Regulatory T cells stimulated by either M2 macrophages ("alternatively activated") or tolerogenic dendritic cells (tDC) migrate to the site of infection, where they act synergistically with M2 and tDC to suppress excessive inflammatory and effector responses.
PMID: 20362587
TRANSPORTsa40sa21
T helper 17 cells (Th17) stimulated by either M1 ("classically activated") macrophages or effector dendritic cells (eDC) migrate from the draning lymph nodes to the site of infection (Lamina Propria), where they act synergistically with M1 and DC to recruit more monocytes.
PMID: 20362587
TRANSPORTsa42sa19
T helper 1 cells stimulated by either M1 ("classically activated") macrophages or effector dendritic cells (eDC) migrate to the site of infection, where they act synergistically with M1 and DC to recruit more monocytes.
PMID: 20362587
TRANSPORTsa47sa15
T helper 2 cells stimulated by either M2 macrophages ("alternatively activated") or tolerogenic dendritic cells (tDC) migrate to the site of infection, where they act synergistically with M2 and tDC to suppress excessive inflammatory and effector responses.
PMID: 20362587
TRANSPORTsa44sa16STATE_TRANSITIONsa753sa752sa640STATE_TRANSITIONsa755sa754sa640STATE_TRANSITIONsa756sa757sa4sa645TRANSPORTsa757sa7STATE_TRANSITIONsa759sa758sa645STATE_TRANSITIONsa758sa759sa29STATE_TRANSITIONsa4sa758STATE_TRANSITIONsa4sa757